Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses

被引:417
作者
Jeffrey, Kate L. [1 ]
Camps, Montserrat
Rommel, Christian
Mackay, Charles R.
机构
[1] Garvan Inst Med Res, Immunol & Inflammat Res Program, Sydney, NSW 2010, Australia
[2] Merck Serono SA, Merck Serono Res Ctr, CH-1202 Geneva, Switzerland
关键词
D O I
10.1038/nrd2289
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Dual-specificity phosphatases (DUSPs) are a subset of protein tyrosine phosphatases, many of which dephosphorylate threonine and tyrosine residues on mitogen-activated protein kinases (MAPKs), and hence are also referred to as MAPK phosphatases (MKPs). The regulated expression and activity of DUSP family members in different cells and tissues controls MAPK intensity and duration to determine the type of physiological response. For immune cells, DUSPs regulate responses in both positive and negative ways, and DUSP-deficient mice have been used to identify individual DUSPs as key regulators of immune responses. From a drug discovery perspective, DUSP family members are promising drug targets for manipulating MAPK-dependent immune responses in a cell-type and disease-context-dependent manner, to either boost or subdue immune responses in cancers, infectious diseases or inflammatory disorders.
引用
收藏
页码:391 / 403
页数:13
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